DOLASETRON - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC POTENTIAL IN THE MANAGEMENT OF NAUSEA AND VOMITING INDUCED BY CHEMOTHERAPY, RADIOTHERAPY OR SURGERY

Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist which has recently become available for clinical use. It i s rapidly converted in vivo to its active major metabolite, hydrodolas etron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of dol asetron were effective in preventing acute chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of vomiting in approximately 50% of patients receiving hi ghly emetogenic cisplatin-containing chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy. I n the latter setting, oral doses of 200mg achieved similar response ra tes. In comparative studies, intravenous dolasetron 1.8 mg/kg was as e ffective as intravenous granisetron 3mg or ondansetron 32mg after high ly emetogenic chemotherapy, and oral dolasetron 200mg was equivalent t o multiple oral doses of ondansetron (3 or 4 doses of 8mg) after moder ately emetogenic chemotherapy. Dolasetron 1.8 mg/kg was superior to me toclopramide in preventing emesis induced by high nose cisplatin or by moderately emetogenic chemotherapy in high risk subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral do lasetron doses ranging from 12.5 to 100mg and 25 to 200mg, respectivel y, were significantly more effective than placebo in preventing postop erative nausea and vomiting (PONV) in female surgical patients. A 50mg intravenous dose was as effective in preventing PONV as ondansetron 4 mg in a mixed-gender group. Intravenously administered dolasetron was also effective in treating established PONV although complete suppress ion of vomiting was achieved in <40% of patients. Dolasetron has a tol erability profile characteristic of this class of compounds, with head ache, dizziness and diarrhoea being the most commonly occurring advers e events in clinical trials. Diarrhoea is not thought to be related to dolasetron administration, being experienced mostly by patients recei ving chemotherapy, Dolasetron and other 5-HT3 receptor antagonists hav e been associated with minor changes in ECG intervals, but these gener ally do not appear to be clinically important. Thus, available evidenc e suggests that dolasetron will provide an alternative to other 5-HT3 receptor antagonists for the management of CINV and PONV. Further stud ies are required to determine whether it offers any advantages over ot her agents in these settings and to determine the optimum dosage for p reventing RINV.